The use of pharmaceutical agents for the prevention and suppression of fertility in warm-blooded female mammals is well-known to the medical arts. At present, the most widely accepted of these pharmaceutical agents comprise mixtures of steroidal estrogens and progestins. The administration of these agents establishes a type of pseudopregnancy thereby preventing normal ovulation from occurring in the female. Although quite effective these agents are not without noticeable side effects. The most common side effects are similar to those symptoms observed during pregnancy and include nausea, gastric disturbances, headache, dizziness, fluid retention, breast discomfort and vascular disorders.
Various other types of contraceptive agents are also known to the art. Estrogens such as diethylstilbesterol and ethinyl estradiol have been used as postcoital contraceptive agents in the so-called "morning after pill." Such agenst are known to interfere with the tubal transport mechanism of the fertilized ovum, resulting in a preliminary expulsion of the fertilized ovum or blastocyst from the Fallopian tubes.
Contraception has also been achieved by disturbing the luteal phase of the uterine lining. A suitably prepared endometrium is necessary for successful implantation or nidation of the blastocyst. Such agents act in a manner which interferes with the formation of the luteal or secretory phase of the uterine lining. Alternatively, such agents may delay or retard the formation of the luteal phase of the uterine endometrium thereby resulting in a desynchronization of uterine development with respect to blastocyst implantation.
Various intrauterine devices have also been employed for the prevention of pregnancy. Such devices require medical insertion and are not a totally effective means for the prevention of pregnancy. Occasionally, devices of this type are involuntarily expelled and will also cause intrauterine irritation and/or bleeding.
Thus, there is a need for both new and better pharmaceutical agents useful in the prevention of pregnancy as well as new and better methods for the administration of existing antifertility agents. In particular there is a need for a highly effective therapeutic measure which can be self-administered and which requires a minimum of drug exposure.
As a result of a long series of investigations, applicants have made the important discovery that 7.alpha.-methyl-estr-5-ene-3.beta.,17.beta.-diol and its 17.beta.-ester derivatives are highly effective contragestative agents useful in those higher primates which have a well-defined menstrual cycle. These compounds are useful in terminating pregnancies at a very early stage. Thus, whereas the estrogen-progestin mixtures now most widely used must be administered for relatively long periods in anticipation of coitus, and whereas postcoital contraceptive agents are administered less frequently but nevertheless administered on a regular basis, the compounds of the present invention are administered on a month to month basis, and then for only a relatively short period of time prior to or about the expected time of menses.
U.S. Pat. No. 3,380,886 represents the closest art known to applicants. Disclosed therein are 7.alpha.-methyl-3.beta.-hydroxy-5-androstenes, in general, and the compound 7.alpha.-methyl-estr-5-ene-3.beta.,17.beta.-diol as having antifertility activity, namely in the inhibition of conception.
Applicants have discovered that the compound, 7.alpha.-methyl-estr-5-ene-3.beta.,17.beta.-diol and its 17-esters, when administered during the implantation stage are highly effective as contragestative agents in terminating an aready existing pregnancy. Thus, it is not necessary to administer these compounds on a day to day basis during most of the menstrual cycle in order to prevent pregnancy from occurring. In contradistinction thereto, it has been discovered that these compounds can be effectively administered subsequent to conception and during the early stages of gestation.